1. Technical Field
The disclosed relates to a pharmaceutical composition with an immunomodulating function, and in particular relates to an extract of Bupleurum with an immunomodulating function.
2. Description of the Related Art
The mechanism for immune disorders has been reported in several studies. Many studies indicate that the over-expressed tumor necrosis factor (TNF-α) is related to immuno-inflammatory diseases, such as rheumatoid arthritis (RA), Crohn's disease, psoriatic arthritis or ankylosing spondylitis.
TNF-α functions like cytokines, modulates cell recruitment, cell proliferation, cell death and immune regulation. At low concentrations in tissues, TNF-α may augment host defense mechanisms against infection. At high concentrations, TNF-α results in excess inflammation leading to organ injuries. Thus, Brennan et al. reported that the removal of excess TNF from the sites of inflammation can treat the immune disorders caused by inflammatory responses (Brennan et al., 1989, Inhibitory effect of TNF-α antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 2, 244-247).
Feldmann et al. reported that TNF plays a particularly important role in the regulation of a cascade of pathogenic events in RA, Crohn's disease, psoriasis and other diseases, exemplified by the rapid induction of cytokines, such as IL-1β and IL-6 (Feldmann et al., 2002, Discovery of TNF-α as a therapeutic target in rheumatoid arthritis: preclinical and clinical studies. Joint Bone Spine 69, 12-18). TNF is over-expressed particularly in animal models of RA (Keffer et al., 1991, Transgenic mice expressing human tumor necrosis factor: a predictive genetic model of arthritis. EMBO J 10, 4025-4031). It has been suggested that a dramatic reduction in serum IL-6 concentrations occurred within 1 day of infliximab therapy was a direct effect of TNF neutralization (Charles et al., 1999, Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-α therapy in rheumatoid arthritis. J Immunol 163, 1521-1528).
Many biologics with inhibition of TNF-α have been produced, such as adalimumab, etanercept, infliximab, DMARDs (for example, methotrexate), or NSAIDs. Due to fast drug efficacy, dramatic effects and well immune toleration, these biologics have become main stream market products. However, biologics are expensive, demanding intravenous administration and have adverse effects, such as risks of inducing undesired immune responses or infection. Developing a drug which is safe for the immune system is challenging.
Bupleurum is a genus of plants used in Chinese medicine for reducing fever, relieving pain, eliminating toxins and reducing inflammation. In Chinese medicine, Bupleurum primarily treats fullness and discomfort in the chest, bitterness in the mouth, dryness in the throat, alternate spell of chill and fever, jaundice, hepatitis, enterogastritis and cholecystitis. The root of Bupleurum is usually used. It has been reported that saikosaponin, longispinogenin, sterols, lipid oil, isoflavones and sugars were isolated from the root of a plant of Bupleurum, and saikosaponin was determined as the chief component. Saikosaponin a and d have been proved to have medicinal effects (Liu S. U., et al., Development Diversity of Bupleurum, Journal of Agricultural Research of China, v. 53, No. 2 (June, 2004)).
Bupleurum has been enthusiastically studied for hepatitis. However, there is no study or journal published implementing the application of Bupleurum to immunomodulation. The inventors have studied the extraction of Bupleurum, wherein the active ingredient of the extract was identified, and the relationship between the active ingredient and TNF-α or IL-6 in vivo was determined. Finally, a novel pharmaceutical composition with an immunomodulation has been developed.